Flow-mediated dilation, carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia

Vigna, Giovanni Battista; Satta, E.; Bernini, Franco; Boarini, S.; Bosi, Cristina; Giusto, L.; Pinotti, Enrico; Tarugi, Patrizia; Vanini, Antonietta; Volpato, Stefano; Zuliani, Giovanni; Favari, Elda

doi:10.1016/j.numecd.2014.02.010

Cited by 29 publications

(35 citation statements)

References 35 publications

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“…Indeed, we found a significant positive relationship between the two parameters. Our observation on the parallel increase in serum total HDL levels and SR‐BI–mediated CEC is not trivial, because certain spontaneous or pharmacologically induced conditions characterized by high serum HDL levels are associated with the production of nonfunctional HDL.…”

Section: Discussionmentioning

confidence: 87%

“…CEC is measured using standardized techniques, and it reflects mainly the ability of HDL to accept cholesterol from macrophages. This HDL functional parameter is correlated directly with indices of vessel health and inversely with cardiovascular risk . MTX treatment is associated with an improvement in serum CEC that is mediated by the cholesterol transporters SR‐BI and ABCG1.…”

Section: Discussionmentioning

confidence: 99%

“…Serum cholesterol efflux capacity (CEC) is the measure of total or transporter‐specific activity of circulating cholesterol acceptors, mainly HDL, through standardized methods . This parameter has been demonstrated to correlate directly with vascular functionality and inversely with atherosclerosis .…”

mentioning

confidence: 99%

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Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

Ronda

Greco

Adorni

et al. 2015

Arthritis & Rheumatology

106

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Objective Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti–tumor necrosis factor α agents in RA is considered secondary to their anti‐inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high‐density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol‐loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The aim of this study was to investigate the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in RA patients and to study the in vitro effects of the two drugs on macrophage cholesterol handling. Methods Sera from RA patients treated with MTX (n = 34) or with adalimumab and MTX (n = 22) obtained before treatment, after 6 weeks of treatment, and after 6 months of treatment were analyzed for CEC and CLC by radioisotopic and fluorometric techniques, respectively. The influence of MTX and adalimumab on macrophage cholesterol efflux and uptake was evaluated in vitro using human THP‐1–derived macrophages. Results MTX treatment was associated with increases in serum HDL, low‐density lipoprotein, and total cholesterol levels and with ATP‐binding cassette G1–mediated and scavenger receptor class B type I (SR‐BI)–mediated increases in CEC; MTX treatment was not associated with modifications in CLC. Adalimumab treatment was associated with increases in serum HDL levels, a transient increase in SR‐BI–mediated CEC, a transient decrease in ATP‐binding cassette A1–mediated CEC, and a significant reduction in CLC; in addition, adalimumab reduced macrophage cholesterol uptake in vitro. Conclusion Antiatherosclerotic activity asso‐ciated with MTX and adalimumab may be mediated by beneficial and complementary effects on lipoprotein functions and on macrophage cholesterol handling. As a whole, these mechanisms may oppose foam cell formation.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

Ronda

Greco

Adorni

et al. 2015

Arthritis & Rheumatology

106

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“…It is well established that hypertension and endothelial dysfunction are closely linked. 28 It is thus relevant to note that Vigna et al 29 reported an inverse correlation between ABCA1-mediated cholesterol efflux and pulse wave velocity, a marker of arterial stiffness, indicating a contribution of HDL efflux capacity to vascular endothelial function. In addition, the association between HDL-mediated vasodilatory effect has been related to the capacity of HDL particles to interact with SR-BI and ABCG1, which are both involved in cholesterol efflux toward mature HDL particles.…”

Section: Discussionmentioning

confidence: 99%

Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis

Gall

Frisdal

Bittar

et al. 2016

JAHA

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BackgroundThe contribution of high‐density lipoprotein to cardiovascular benefit is closely linked to its role in the cellular cholesterol efflux process; however, various clinical and biochemical variables are known to modulate the overall cholesterol efflux process. The aim of this study was to evaluate the extent to which clinical and biological anomalies associated with the establishment of the metabolic syndrome modulate cholesterol efflux capacity and contribute to development of atherosclerosis.Methods and ResultsThis study involved patients (n=1202) displaying atherogenic dyslipidemia in primary prevention who were referred to our prevention center. Among these patients, 25% presented at least 3 criteria of the metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III. We measured the capacity of 40‐fold diluted serum to mediate cholesterol efflux from cholesterol‐loaded human THP‐1 macrophages. Cholesterol efflux capacity was reduced progressively by 4% to 11% (P<0.0001) as a function of the increasing number of coexisting criteria for the metabolic syndrome from 1 to 5. This observation was primarily related to reductions in scavenger receptor class B member 1 and ATP binding cassette subfamily G member 1–dependent efflux. Multivariate analyses indicate that serum efflux capacity was significantly associated with established metabolic syndrome (odds ratio 0.45; 95% CI 0.28–0.72; P=0.009) independent of age, low‐density lipoprotein cholesterol, status with regard to lipid‐lowering therapy, smoking status, and alcohol consumption.ConclusionsOur study revealed that individual criteria of metabolic syndrome are closely related synergistically to cholesterol efflux capacity. In addition, established metabolic syndrome and cholesterol efflux capacity were independently associated with clinical features of atherosclerosis.

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“…Serum was depleted of apoB-containing lipoproteins in order to isolate the serum HDL fraction as previously described 16 . ApoB-depleted serum CEC was determined in human monocytes-derived macrophages THP-1 cultured in the presence of 100 ng/ml PMA for 72 hours to allow differentiation into macrophages.…”

Section: Cholesterol Loading Capacitymentioning

confidence: 99%

Lomitapide affects HDL composition and function

et al. 2016

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Flow-mediated dilation, carotid wall thickness and HDL function in subjects with hyperalphalipoproteinemia

Cited by 29 publications

References 35 publications

Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism

Association of Cholesterol Efflux Capacity With Clinical Features of Metabolic Syndrome: Relevance to Atherosclerosis

Lomitapide affects HDL composition and function

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